Pladienolide B represented by Formula (1′):
and Pladienolide D represented by Formula (2′):
are 12 membered-ring macrolide compounds found by Sakai et al. in a culture of Streptomyces sp. Mer-11107 strain, and are known to have excellent anti-tumor activity (See Patent Document 1).
However, total synthesis of pladienolide B and pladienolide D has not been reported at all till now, and the purification of the above culture has been the only process for acquiring pladienolide B and pladienolide D. In addition, there was a problem that there was limitation in the structural variety of derivatives obtained by chemical conversion from pladienolide B and pladienolide D themselves which were fermentation products. Furthermore, absolute configuration of pladienolide B and pladienolide D has not yet been determined (See Patent Document 1), and the determination thereof has been a problem to be solved. Accordingly, establishment of a process for total synthesis of pladienolide B and pladienolide D has been strongly desired from the viewpoints of (1) supply of pladienolide B and pladienolide D by chemical synthesis, (2) synthesis of various pladienolide derivatives and (3) determination of absolute configuration of pladienolide B and pladienolide D.
In the meantime, although compounds analogous to pladienolide B and pladienolide D in structure were disclosed in Patent Documents 1 to 5, total synthesis of these compounds was not disclosed in any of the documents.
[Patent Document 1] WO02/60890 pamphlet
[Patent Document 2] JP-A-04-352783
[Patent Document 3] WO03/099813 pamphlet
[Patent Document 4] WO2004/011459 pamphlet
[Patent Document 5] WO2004/011611 pamphlet